Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty patients with locally advanced or metastatic breast cancer were treated with four cycles of ifosfamide/mesna 5 g m-2 and epirubicin 60 mg m-2 every 14 days with granulocyte colony-stimulating factor (G-CSF, Filgrastim). Complete remission occurred in six out of the 20 patients (30%, 95% confidence interval 12-54%) and there were 12 partial responders (60%, 95% confidence interval 37-81%), thus giving an overall response rate of 90% (95% confidence interval 63-97%). Two patients had progressive disease. The median duration of response for those patients with metastatic disease was 7.3 (1.3-20.1+) months. The median survival time for these patients was 15 (5.3-27.9+) months. Of the four patients treated with locally advanced disease three achieved a complete clinical response and one a partial response. Three out of four of these patients subsequently underwent a mastectomy, and in one of these no viable tumour was seen. Our conclusion is that this regimen is excellent palliation for metastatic disease and possibly useful neoadjuvant treatment.
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PMID:The use of granulocyte colony-stimulating factor to deliver four cycles of ifosfamide and epirubicin every 14 days in women with advanced or metastatic breast cancer. 753 18

The restoration of hematopoiesis after high-dose chemotherapy may be accelerated by the use of stem cells from the bone marrow (BM) or peripheral blood. Numerous reports utilizing mobilized peripheral blood progenitor cells (PBPC) for stem cell rescue have shown that PBPC are sufficient to restore hematopoiesis, but there are little data comparing the recovery among patients treated with various stem cell sources. We reviewed the clinical outcomes of 69 women at our institution who were treated for locally advanced or metastatic breast cancer with high-dose cyclophosphamide (CY) and thiotepa and autologous stem cell and growth factor support. Of the 43 patients with normal BM, 19 received BM alone and 24 received BM plus G-CSF mobilized PBPC. Of the 26 patients with evidence of metastatic disease in the BM, or evidence of fibrosis and hypocellularity, 15 received CY-mobilized PBPC and 11 received CY/G-CSF-mobilized PBPC. Of the marrow-negative patients, those receiving BM alone had significantly longer (P < 0.001) granulocyte recovery (absolute neutrophil count > 500 x 10(6)/l) and platelet recovery (platelets > 50 x 10(9)/l) compared with BM + G-CSF-mobilized PBPC. They also had significantly longer (P < 0.001) durations of antibiotic and amphotericin usage, increased transfusion requirements and longer hospitalizations. Of the marrow-positive patients, there was a slightly shortened granulocyte recovery, shortened hospital stays and lessened amphotericin usage in the patients who received CY/G-CSF-mobilized PBPC compared with the CY-mobilized patients. Although the number of harvested mononuclear cells differed significantly between the groups, this did not correlate with the time to hematopoietic recovery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Source of stem cells impacts on hematopoietic recovery after high-dose chemotherapy. 758 Oct 92

The search for new active agents and strategies to improve the prognosis for patients with stage IV breast cancer has led to examination of paclitaxel. Several clinical trials have been undertaken to determine its optimal use and clarify its role in the treatment of breast cancer and other malignancies. Several phase II trials involving breast cancer patients with limited prior therapy have yielded overall response rates (complete response and partial response) of 44% to 62% among women receiving paclitaxel. Treatment was generally well tolerated, with febrile neutropenia the most common side effect. An interim analysis of the European-Canadian Randomized Trial in Metastatic Breast Cancer demonstrated safety and efficacy of paclitaxel in a multicenter setting. Among the 234 patients evaluable for response, 29% (34/117) responded at 175 mg/m2 paclitaxel and 22% responded (26/117) at 135 mg/m2. Treatment was well tolerated at both dose levels; responses continue to evolve in patients who remain on study. Among patients with extensive prior therapy (> 2 prior regimens for stage IV disease), paclitaxel also has demonstrated safety and efficacy. At Memorial Sloan-Kettering Cancer Center, responses were noted among 36% of patients who had received two prior treatments and 21% of those who had received 3 or more. Paclitaxel was administered at 200 mg/m2 plus G-CSF. Other studies involving heavily pretreated patients yielded overall response rates as high as 53%. The concerns about cross-resistance between paclitaxel and doxorubicin (or other agents for which resistance is thought to be at least partly due to P-glycoprotein-mediated pleiotropic drug resistance) also are addressed.
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PMID:Single-agent use of Taxol (paclitaxel) in breast cancer. 786 28

Taxol is a cytostatic agent of plant origin with a complex structure and a special mode of action. Owing to the small content of this substance in the bark of the Pacific yew, from which Taxol is derived, it has only been available on a limited scale. Hitherto, Taxol's chemical structure has precluded the synthesis of large quantities of this cytostatic agent. Analogue substances can be obtained from the needles of the yew, although more efficient methods are needed for the manufacture of this medicine on a commercial scale. The present paper summarises the results of preclinical and clinical studies of patients suffering from ovarian and breast cancer. In phase I studies, it was possible to delineate the side effect profile of Taxol, neutropenia being dose-limiting in most investigations. The efficacy of Taxol on patients with ovarian cancer was initially demonstrated in phase I studies. These results led to phase II studies, in which response rates of 20-36% were obtained on patients with relapsing or therapy-refractory ovarian carcinomas. In phase III studies, the efficacy of Taxol combined with cisplatinum is currently being compared with the classical regimen of cisplatinum/cyclophosphamide. Further studies are under way testing Taxol in combination with G-CSF and cisplatinum. As a supplement to intravenous Taxol therapy, initial experience with intraperitoneal Taxol treatment is now available. Taxol's cytostatic efficacy has also been confirmed in the treatment of patients suffering from metastatic breast cancer with remission rates of 56-62%. Taxol is an important new cytostatic agent for the treatment of ovarian and breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Taxol--a new cytostatic drug for therapy of ovarian and breast cancer]. 791 12

At the low-to-moderate doses that are recommended, paclitaxel is a well-tolerated drug. Although adverse reactions do occur, most of these are manageable and do not have a long-lasting effect on the patients' quality of life. The starting dose of paclitaxel, as approved by the Food and Drug Administration for refractory ovarian cancer, is 135 mg/m2. A slightly higher dose (175 mg/m2) is being investigated for heavily pretreated patients with metastatic breast cancer. In the investigational setting, the highest dose that may safely be administered when paclitaxel is used as a single agent is 250 mg/m2 for minimally pretreated patients. If G-CSF is also given, the same dose may safely be administered to heavily pretreated patients. When paclitaxel is administered in combination with cisplatin, a dose of 135 mg/m2 may safely be given prior to cisplatin, which is administered at a dose of 75 mg/m2. These dose levels may be increased when G-CSF is also used. Dose modifications should be considered only in patients who experience severe neutropenia or neurotoxicity. Patients who received high doses of paclitaxel in Phase II trials frequently required dose reductions. However, when the drug is administered at the recommended dose of 135 mg/m2, neutropenia does not often necessitate further dose reduction. Hematopoietic growth factors, such as G-CSF, seem to be helpful in preventing prolonged grade IV and febrile neutropenia, and in avoiding treatment delays for longer than one week.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Patient care issues: the management of paclitaxel-related toxicities. 791 56

Cytopenia after high-dose chemotherapy and autologous stem cell reinfusion is a major cause of morbidity. Ex vivo cultured expansion and differentiation of CD34+ peripheral blood progenitor cells (PBPC) to neutrophil precursors may shorten the neutropenic period further. We explored the use of these ex vivo cultured PBPCs in nine patients with metastatic breast cancer. All underwent PBPC mobilization with cyclophosphamide, VP-16, and G-CSF. Subsequently, they underwent four to five apheresis procedures. One apheresis product from each patient was prepared using the Isolex 300 Magnetic Cell Separation System (Baxter Immunotherapy, Irvine, CA) to obtain CD34+ cells. These cells were then cultured in gas permeable bags containing serum-free X-VIVO 10 (BioWhittaker, Walkersville, MD) medium supplemented with 1% human serum albumin and 100 ng/mL PIXY321. At day 12 of culture the mean fold expansion was 26x with a range of 6 to 64x. One patient's cells did not expand because of a technical difficulty. The final cell product contained an average of 29.3% CD15+ neutrophil precursors with a range of 18.5% to 48.1%. The patients underwent high-dose chemotherapy with cyclophosphamide, carboplatin, and thiotepa. On day 0, the cryopreserved PBPCs were reinfused and on day +1 the 12-day cultured cells were washed, resuspended, and reinfused into eight of nine patients. One patient was not infused with cultured cells. The mean number of cultured cells reinfused was 44.6 x 10(6) cells/kg with a range of 0.8 to 156.6 x 10(6) cells/kg. No toxicity was observed after reinfusion. The eight patients have recovered absolute neutrophil counts > 500/microL on a median of 8 days (range 8 to 10 days); the median platelet transfusion independence occurred on day 10 (range 8 to 12 days) and platelet counts > 50,000/microL were achieved by day 12 (range 9 to 14) for the seven patients whose platelet counts could be determined. Expanded CD34+ selected PBPC can be obtained and safely reinfused into patients.
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PMID:Selection and expansion of peripheral blood CD34+ cells in autologous stem cell transplantation for breast cancer. 863 12

Peripheral blood progenitor cell (PBPC) autografts have a number of advantages over autologous bone marrow transplantation (ABMT) as haematopoietic support after high-dose chemotherapy in patients with breast cancer. These may include less contamination by tumour cells, reduced morbidity and mortality and additional dose escalation of chemotherapy. A dose-escalation study is described using recombinant granulocyte colony-stimulating factor (G-CSF; filgrastim) primed PBPC support and post-infusion filgrastim for patients with high-risk or metastatic breast cancer. The regimen involved the use of cyclophosphamide, thiotepa and carboplatin at five dose levels. The main problem to emerge was organ toxicity induced by chemotherapy or sepsis. Patients receiving higher levels of chemotherapy were therefore allocated or not to an additional regimen involving pentoxifylline, ciprofloxacin and dexamethasone in an attempt to inhibit tumour necrosis factor alpha (TNF-alpha) which is believed to be one of the principal mediators of chemotherapy-related organ toxicity. The incidence of bilirubin elevations, weight gain > 5% and veno-occlusive disease (VOD) was lower in patients receiving the 'anti-TNF' therapy. The simultaneous use of PBPC support and 'anti-TNF' therapy therefore allows a substantial increase in chemotherapy dosage. Further studies with larger patient numbers are required to show whether this decreased toxicity also produces increased patient survival.
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PMID:High-dose chemotherapy for breast cancer: clinical advantages of autologous peripheral blood progenitor cells (PBPC) compared with autologous bone marrow transplantation (ABMT). 875 Jan 43

Tandem cycles of myeloablative chemotherapy can increase dose intensity and total dose of chemotherapy, but sufficient numbers of progenitor cells must be collected to ensure hematologic recovery after each treatment. This study was undertaken to determine if two courses of mobilizing chemotherapy given 4 weeks apart using cyclophosphamide 4000 mg/m2 and etoposide 400 mg/m2, combined with G-CSF 5-10 mg/kg on days 3-16 could each provide sufficient numbers of peripheral blood progenitor cells to support tandem cycles of myeloablative chemotherapy in 20 patients with stage IV breast cancer. Leukapheresis of blood with WBC > 1000/mm3 was performed daily for up to five collections (days 12-16), and mononuclear cells, CFU-GM, and CD34+ cells were compared between the first and second collections. The second course of mobilizing treatment resulted in similar numbers of mononuclear cells collected but far fewer CFU-GM and CD34+ progenitor cells. This prevented using the second collection of progenitor cells as the sole source for the second transplant. The data suggest that a second course of cyclophosphamide, etoposide, and G-CSF given 4 weeks after the first leads to progenitor cell depletion, and efforts to increase the yield of blood-derived progenitors should focus on the initial mobilizing procedure.
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PMID:Impaired stem cell collection by consecutive courses of high-dose mobilizing chemotherapy using cyclophosphamide, etoposide, and G-CSF. 881 94

Infusion of thawed cryopreserved autologous stem cells (SC) is associated with a variety of complications due to the presence of dimethyl sulfoxide (DMSO) and free hemoglobin and to volume overload. Commonly, the DMSO is not removed before infusion for fear that prolonged in vitro exposure of the cells to DMSO leads to loss of clonogenic activity. We describe a simple technique for the substantial reduction in volume and DMSO content of bone marrow (BM) and peripheral blood stem cell (PBSC) suspensions. Sixty-five patients were transplanted with thawed, volume-reduced SC cryopreserved according to Stiff et al. Semiautomated volume reduction was performed on a COBE 2991 cell processor. The median volumes of cryopreserved SC were 1152 ml and 933 ml for the pools of PBSC products and the mixed pools of BM and PBSC, respectively, whereas the volume of SC infused was 153 ml (78% reduction). There were no differences in cell recoveries between PBSC and BM (98%). Only 2 patients demonstrated minimal side effects during infusion. A cohort of 16 metastatic breast cancer patients underwent PBSC harvests following chemotherapy/G-CSF priming and subsequent autotransplantation. Median time to an absolute neutrophil count > 500/microliters was 8 days (range 6-14 days), and median time to a platelet count > 20,000/microliters was 11 days (range 6-18 days). Volume reduction of SC products without the risk of graft failure was performed simply and resulted in few complications during infusion.
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PMID:A semiautomated technique for volume reduction of stem cell suspensions for autotransplantation. 884 15

Autologous peripheral blood progenitor cells (PBPC) rescue after high-dose chemotherapy has been used progressively as a form of treatment in some solid and hematologic tumors. This increasing use can be explained by both advantages of PBPC rescue over bone marrow rescue (decrease in the duration of marrow aplasia, reduction of platelet transfusions, earlier discharge from hospital, potential use in patients with inadequate bone marrow reserve) and the low number of aphereses (one or two) needed to collect a sufficient number of progenitor cells for autografting. High-dose chemotherapy is likely to be increasingly used after the results of two recently reported studies in which treatment with high-dose compared with standard-dose chemotherapy increases overall survival in metastatic breast cancer patients and relapsed lymphoma patients. After the initial use of unselected mobilizing regimens regardless of the patient characteristics and the tumor type, now it seems more useful to optimize this approach. Mobilization of PBPC can be obtained by several approaches. Moderate or high doses of single agent alone (e.g. cyclophosphamide 4-7 g/m2) or some hematopoietic growth factors alone (e.g. G-CSF, GM-CSF) have been proven to be adequate mobilizing agents. However, the use of hematopoietic growth factors alone may disadvantageously delay the start of an effective chemotherapy. An efficient mobilizing regimen requires the use of both chemotherapy and hematopoietic growth factors: the efficiency of mobilization was greater and with less side effects than chemotherapy alone. It was postulated that PBPC mobilization could be achieved only at hematopoietic recovery following myeloablative chemotherapy. Recently, it has been demonstrated that some standard-dose chemotherapy regimens associated with hematopoietic growth factors are efficient priming agents. We reported that standard-dose CEF chemotherapy plus filgrastim is a disease specific regimen (breast cancer) allowing PBPC mobilization without any relevant toxicity. The maximum release of PBPC has been observed at day 11. The optimal time for PBPC collection is predictable and aphereses can be guided by WBC counts. In conclusion, both standard and high dose chemotherapy are effective priming regimens. So presently a mobilizing regimen should be an effective disease specific chemotherapy program and should contain a hematopoletic growth factor. The choice between standard and high-dose chemotherapy can be based on patients characteristic and disease status.
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PMID:[Mobilization of peripheral blood stem cells with conventional chemotherapy]. 892 33


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